White matter changes in the trigeminal spinal tract in chronic migraineurs: an ex vivo study combining ultra-high-field diffusion tensor imaging and polarized light imaging microscopy

Chronic migraine (CM) is a disabling neurologic disorder that affects approximately 2% of the general population. Neuroimaging studies show functional involvement of trigeminal structures, such as the trigeminal spinal nucleus (Sp5) in migraine. However, structural changes in the Sp5 and the afferent trigeminal spinal tract (sp5) have never been found. The aim of this study was to test the hypothesis that white matter changes in the sp5 are a key feature of brain alterations in patients with CM. We used diffusion magnetic resonance imaging and polarized light imaging of postmortem brainstem specimens from healthy controls (n = 5) and patients with CM (n = 5) to study white matter alterations in the sp5. Within the sp5, diffusion magnetic resonance imaging metrics included fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity values. Polarized light imaging was used to assess myelin density by a measure of the retardance values in the sp5. This study provides histological evidence that structural alterations occur in the sp5 in patients with CM as compared with healthy controls. Myelin density, as assessed by retardance values, showed to be higher, and a corresponding increase in fractional anisotropy values was observed. In addition, accompanying decreases in mean diffusivity, axial diffusivity, and radial diffusivity values were observed. This study shows that the sp5 undergoes neuroplastic changes, a feature which substantiates evidence for the hyperactivity of the Sp5 in patients with migraine. More insights are needed to observe whether these changes only occur in patients with CM.